Tissue adhesives have many potential medical applications, including wound closure, supplementing or replacing sutures or staples in internal surgical procedures, adhesion of synthetic onlays or inlays to the cornea, drug delivery devices, and as anti-adhesion barriers to prevent post-surgical adhesions. Conventional tissue adhesives are generally not suitable for a wide range of adhesive applications. For example, cyanoacrylate-based adhesives have been used for topical wound closure, but the release of toxic degradation products limits their use for internal applications. Fibrin-based adhesives are slow curing, have poor mechanical strength, and pose a risk of viral infection. Additionally, fibrin-based adhesives do not bond covalently to the underlying tissue.
Several types of hydrogel tissue adhesives have been developed, which have improved adhesive and cohesive properties and are nontoxic (see for example Sehl et al., U.S. Patent Application Publication No. 2003/0119985, and Goldmann, U.S. Patent Application Publication No. 2005/0002893). These hydrogels are generally formed by reacting a component having nucleophilic groups with a component having electrophilic groups, which are capable of reacting with the nucleophilic groups of the first component, to form a crosslinked network via covalent bonding. However, these hydrogels typically swell, dissolve away too quickly, or lack sufficient adhesion or mechanical strength, thereby decreasing their effectiveness as surgical adhesives.
Kodokian et al. (copending and commonly owned U.S. Patent Application Publication No. 2006/0078536) describe hydrogel tissue adhesives formed by reacting an oxidized polysaccharide with a water-dispersible, multi-arm polyether amine. These adhesives provide improved adhesion and cohesion properties, crosslink readily at body temperature, maintain dimensional stability initially, do not degrade rapidly, and are nontoxic to cells and non-inflammatory to tissue. However, for certain applications such as use as a hemostat sealant or to prevent undesired tissue-to-tissue adhesions resulting from trauma or surgery, tissue adhesives that are fast gelling, have good adhesive and cohesive strength, and degrade more rapidly are needed. It can be difficult to decrease the degradation time of the hydrogel without an undesired increase in the gelation time.
Figuly et al. (copending and commonly owned U.S. patent application Ser. No. 12/145,737) describe a method for extending the gelation time of an oxidized polysaccharide to react with a water-dispersible, multi-arm polyether amine to form a hydrogel. The method also decreases the degradation time of the hydrogel. The method utilizes a chemical additive that reacts with the functional groups of the oxidized polysaccharide or the water-dispersible, multi-arm polyether amine, thereby reducing the number of groups available for crosslinking.
Therefore, the need exists for a hydrogel tissue adhesive that is fast gelling, has good adhesive and cohesive strength, and degrades more rapidly than conventional hydrogel adhesives.